ABSTRACT
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), especially the USA300 pulsotype, is a frequent cause of skin and soft tissue infections and severe pneumonia. Despite appropriate antibiotic treatment, complications are common and pneumonia is associated with high mortality. S. aureus strains express multiple cytotoxins, including alpha-hemolysin (Hla) and up to five bicomponent leukocidins that specifically target phagocytic cells for lysis. CA-MRSA USA300 strains carry the genes for all six cytotoxins. Species specificity of the leukocidins greatly contributes to the ambiguity regarding their role in S. aureus pathogenesis. We performed a comparative analysis of the leukocidin susceptibility of human, rabbit, and mouse polymorphonuclear leukocytes (PMNs) to assess the translational value of mouse and rabbit S. aureus models. We found that mouse PMNs were largely resistant to LukSF-PV, HlgAB, and HlgCB and susceptible only to LukED, whereas rabbit and human PMNs were highly sensitive to all these cytotoxins. In the rabbit pneumonia model with a USA300 CA-MRSA strain, passive immunization with a previously identified human monoclonal antibody (MAb), Hla-F#5, which cross-neutralizes Hla, LukSF-PV, HlgAB, HlgCB, and LukED, provided full protection, whereas an Hla-specific MAb was only partially protective. In the mouse USA300 CA-MRSA pneumonia model, both types of antibodies demonstrated full protection, suggesting that Hla, but not leukocidin(s), is the principal virulence determinant in mice. As the rabbit recapitulates the high susceptibility to leukocidins characteristic of humans, this species represents a valuable model for assessing novel, cytotoxin-targeting anti-S. aureus therapeutic approaches.
Subject(s)
Antibodies, Neutralizing/pharmacology , Bacterial Toxins/immunology , Hemolysin Proteins/immunology , Leukocidins/immunology , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Pneumonia, Necrotizing/prevention & control , Pneumonia, Staphylococcal/prevention & control , Animals , Antibodies, Monoclonal/pharmacology , Community-Acquired Infections/microbiology , Disease Models, Animal , Female , Humans , Leukocidins/pharmacology , Male , Mice, Inbred BALB C , Neutrophils/drug effects , Neutrophils/microbiology , Pneumonia, Necrotizing/immunology , Pneumonia, Necrotizing/microbiology , Pneumonia, Necrotizing/mortality , Pneumonia, Staphylococcal/immunology , RabbitsABSTRACT
Community-acquired methicillin-resistant Staphylococcus aureus is the first cause of skin and soft tissue infections, but can also produce severe diseases such as bacteremia, osteomyelitis and necrotizing pneumonia. Some S. aureus lineages have been described in cases of necrotizing pneumonia worldwide, usually in young, previously healthy patients. In this work, we describe a fatal case of necrotizing pneumonia due to community-acquired methicillin-resistant S. aureus clone ST30-SCCmecIVc-spat019-PVL positive in an immunocompetent adult patient.
Staphylococcus aureus resistente a meticilina adquirido en la comunidad es la primera causa de infecciones de piel y partes blandas, aunque también puede producir infecciones graves, como bacteriemia, osteomielitis y neumonía necrotizante. Algunos linajes de S. aureus se han asociado a casos de neumonía necrotizante en el mundo, generalmente en pacientes jóvenes previamente sanos. En este trabajo comunicamos un caso fatal de neumonía necrotizante causado por el clon de S. aureus resistente a meticilina adquirido en la comunidad ST30-SCCmecIVc-spat019-LPV positivo, en un paciente adulto inmunocompetente
